Jessica E. Nevins

In vivo lamina cribrosa micro-architecture in healthy and glaucomatous eyes as assessed by optical coherence tomography.

PURPOSE The lamina cribrosa (LC) is a prime location of glaucomatous damage. The purpose of this study was to compare LC 3-dimensional micro-architecture between healthy and glaucomatous eyes in vivo by using optical coherence tomography (OCT). METHODS Sixty-eight eyes (19 healthy and 49 glaucomatous) from 47 subjects were scanned in a 3.5 × 3.5 × 3.64-mm volume (400 × 400 × 896 pixels) at the optic nerve head by using swept-source OCT. The LC micro-architecture parameters were measured on the visible LC by an automated segmentation algorithm. The LC parameters were compared to diagnosis and visual field mean deviation (VF MD) by using a linear mixed effects model accounting for age. RESULTS The average VF MD for the healthy and glaucomatous eyes was -0.50 ± 0.80 dB and -7.84 ± 8.75 dB, respectively. Beam thickness to pore diameter ratio (P = 0.04) and pore diameter standard deviation (P < 0.01) were increased in glaucomatous eyes. With worse MD, beam thickness to pore diameter ratio (P < 0.01), pore diameter standard deviation (P = 0.05), and beam thickness (P < 0.01) showed a statistically significant increase while pore diameter (P = 0.02) showed a significant decrease. There were no significant interactions between any of the parameters and age (all P > 0.05). CONCLUSIONS Glaucomatous micro-architecture changes in the LC, detected by OCT analysis, reflect beams remodeling and axonal loss leading to reduction in pore size and increased pore size variability.

Macular assessment using optical coherence tomography for glaucoma diagnosis

Optical coherence tomography (OCT) is an interferometry-based imaging modality that generates high-resolution cross-sectional images of the retina. Circumpapillary retinal nerve fibre layer (cpRNFL) and optic disc assessments are the mainstay of glaucomatous structural measurements. However, because these measurements are not always available or precise, it would be useful to have another reliable indicator. The macula has been suggested as an alternative scanning location for glaucoma diagnosis. Using time-domain (TD) OCT, macular measurements have been shown to provide good glaucoma diagnostic capabilities. Performance of cpRNFL measurement was generally superior to macular assessment. However, macular measurement showed better glaucoma diagnostic performance and progression detection capability in some specific cases, which suggests that these two measurements may be combined to produce a better diagnostic strategy. With the adoption of spectral-domain OCT, which allows a higher image resolution than TD-OCT, segmentation of inner macular layers becomes possible. The role of macular measurements for detection of glaucoma progression is still under investigation. Improvement of image quality would allow better visualisation, development of various scanning modes would optimise macular measurements, and further refining of the analytical algorithm would provide more accurate segmentation. With these achievements, macular measurement can be an important surrogate for glaucomatous structural assessment.

Automated lamina cribrosa microstructural segmentation in optical coherence tomography scans of healthy and glaucomatous eyes

We demonstrate an automated segmentation method for in-vivo 3D optical coherence tomography (OCT) imaging of the lamina cribrosa (LC). Manual segmentations of coronal slices of the LC were used as a gold standard in parameter selection and evaluation of the automated technique. The method was validated using two prototype OCT devices; each had a subject cohort including both healthy and glaucomatous eyes. Automated segmentation of in-vivo 3D LC OCT microstructure performed comparably to manual segmentation and is useful for investigative research and in clinical quantification of the LC.

IOP Elevation Reduces Schlemm's Canal Cross-Sectional Area

PURPOSE Previously, we demonstrated reduced Schlemms canal cross-sectional area (SC-CSA) with increased perfusion pressure in a cadaveric flow model. The purpose of the present study was to determine the effect of acute IOP elevation on SC-CSA in living human eyes. METHODS The temporal limbus of 27 eyes of 14 healthy subjects (10 male, 4 female, age 36 ± 13 years) was imaged by spectral-domain optical coherence tomography at baseline and with IOP elevation (ophthalmodynamometer set at 30-g force). Intraocular pressure was measured at baseline and with IOP elevation by Goldmann applanation tonometry. Vascular landmarks were used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemms canal CSA at five locations within a 1-mm length of SC was measured in ImageJ as described previously. A linear mixed-effects model quantified the effect of IOP elevation on SC-CSA. RESULTS The mean IOP increase was 189%, and the mean SC-CSA decrease was 32% (P < 0.001). The estimate (95% confidence interval) for SC-CSA response to IOP change was -66.6 (-80.6 to -52.7) μm(2)/mm Hg. CONCLUSIONS Acute IOP elevation significantly reduces SC-CSA in healthy eyes. Acute dynamic response to IOP elevation may be a useful future characterization of ocular health in the management of glaucoma.

Repeatability of in vivo 3D lamina cribrosa microarchitecture using adaptive optics spectral domain optical coherence tomography

We demonstrate the repeatability of lamina cribrosa (LC) microarchitecture for in vivo 3D optical coherence tomography (OCT) scans of healthy, glaucoma suspects, and glaucomatous eyes. Eyes underwent two scans using a prototype adaptive optics spectral domain OCT (AO-SDOCT) device from which LC microarchitecture was semi-automatically segmented. LC segmentations were used to quantify pore and beam structure through several global microarchitecture parameters. Repeatability of LC microarchitecture was assessed qualitatively and quantitatively by calculating parameter imprecision. For all but one parameters (pore volume) measurement imprecision was <4.7% of the mean value, indicating good measurement reproducibility. Imprecision ranged between 27.3% and 54.5% of the population standard deviation for each parameter, while there was not a significant effect on imprecision due to disease status, indicating utility in testing for LC structural trends.

Characterisation of Schlemm's canal cross-sectional area

Purpose To compare three methods of Schlemms canal (SC) cross-sectional area (CSA) measurement. Methods Ten eyes (10 healthy volunteers) were imaged three times using spectral-domain optical coherence tomography (Cirrus HD-OCT, Zeiss, Dublin, California, USA). Aqueous outflow vascular structures and SC collector channel ostia were used as landmarks to identify a reference location within the limbus. SC CSA was assessed within a 1 mm segment (±15 frames of the reference, 31 frames in all) by three techniques. (1) Using a random number table, SC CSA in five random frames from the set of 31 surrounding the reference were measured and averaged. (2) The most easily visualised SC location (subjective) was measured, and (3) SC CSA was measured in all 31 consecutive B-scans, and averaged. (comprehensive average, gold standard). Subjective and random CSAs were compared with the comprehensive by general estimating equation modelling, and structural equation modelling quantified agreement. Results The average from five random locations (4175±1045 µm2) was not significantly different than that obtained from the gold standard comprehensive assessment (4064±1308 µm2, p=0.6537). Subjectively located SC CSA (7614±2162 µm2) was significantly larger than the comprehensive gold standard SC CSA (p<0.0001). The average of five random frames produced significantly less bias than did subjective location, yielding a calibration line crossing the ‘no-bias’ line. Discussion Subjectively located SC CSA measurements produce high estimates of SC CSA. SC assessed by measuring five random locations estimate CSA was similar to the gold standard estimate.

Reproducibility of In-Vivo OCT Measured Three-Dimensional Human Lamina Cribrosa Microarchitecture

Purpose To determine the reproducibility of automated segmentation of the three-dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using optical coherence tomography (OCT). Methods Thirty-nine eyes (8 healthy, 19 glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using swept-source (SS−) OCT in a 3.5×3.5×3.64 mm (400×400×896 pixels) volume centered on the optic nerve head, with the focus readjusted after each scan. The LC was automatically segmented and analyzed for microarchitectural parameters, including pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore area, beam thickness, beam thickness SD, and beam thickness to pore diameter ratio. Reproducibility of the parameters was assessed by computing the imprecision of the parameters between the scans. Results The automated segmentation demonstrated excellent reproducibility. All LC microarchitecture parameters had an imprecision of less or equal to 4.2%. There was little variability in imprecision with respect to diagnostic category, although the method tends to show higher imprecision amongst healthy subjects. Conclusion The proposed automated segmentation of the LC demonstrated high reproducibility for 3D LC parameters. This segmentation analysis tool will be useful for in-vivo studies of the LC.